Enterococcus is a genus of oval-shaped gram-positive cocci that are arranged in pairs or short chains. Distinguishing factors include optochin resistance and the presence of pyrrolidonyl arylamidase (PYR) and Lancefield D antigen. Enterococcus is part of the normal flora of the human GI tract and is frequently involved in nosocomial infections in critically ill or immunocompromised patients, especially those treated with prolonged courses of antibiotics. Common enterococcal infections include urinary tract infections, endocarditis, and intra-abdominal infections. Enterococci are notorious for their intrinsic and acquired resistance to multiple antimicrobials, which makes treatment of enterococcal infections particularly challenging.

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Microbiology flowchart gram-positive bacteria classification

Gram-positive bacteria:
Most bacteria can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thick layer of peptidoglycan retain the crystal violet stain utilized in Gram staining but are not affected by the safranin counterstain. These bacteria appear as purple-blue on the stain, indicating that they are gram positive. The bacteria can be further classified according to morphology (branching filaments, bacilli, and cocci in clusters or chains) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The cocci can also be further identified. Staphylococci can be narrowed down on the basis of the presence of the enzyme coagulase and on their sensitivity to the antibiotic novobiocin. Streptococci are grown on blood agar and classified on the basis of which form of hemolysis they employ (α, β, or γ). Streptococci are further narrowed on the basis of their response to the pyrrolidonyl-β-naphthylamide (PYR) test, their sensitivity to specific antimicrobials (optochin and bacitracin), and their ability to grow on sodium chloride (NaCl) media.

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General Characteristics

Enterococci (formerly classified as group D streptococci) are part of the normal flora of the human GI tract. Fewer than ⅓ of the known species are responsible for clinically significant human disease. 

Genus characteristics

  • Oval-shaped gram-positive cocci 
  • Arranged in pairs or short chains
  • Facultative anaerobes
  • Catalase-negative
  • Optochin-resistant
  • Pyrrolidonyl arylamidase (PYR)–positive
  • Possess Lancefield group D antigen (hence, previously classified as group D streptococci)
  • Can be cultured in bile media and 6.5% NaCl
  • Clinically significant human pathogens (most common):
    • Enterococcus faecalis 
    • E. faecium
Enterococcus faecalis

Enterococcus faecalis

Image: “Enterococcus faecalis20023-300” by Gzuckier. License: Public Domain


Enterococci most commonly appear in nosocomial infections.

  • Reservoir: human GI tract
  • Transmission:
    • Translocation from colonization site in the colonized patient (frequently associated with GI and genitourinary procedures)
    • Transmission to health care workers and other patients through direct contact, fecal–oral transmission, or fomites
  • Virulence factors:
    • Antimicrobial resistance:
      • Intrinsic (beta-lactam antibiotics (through penicillin-binding proteins), trimethoprim–sulfamethoxazole, low levels of clindamycin and aminoglycosides)
      • Acquired (beta-lactam antibiotics (through beta-lactamases), high-level aminoglycosides, tetracycline, fluoroquinolones, rifampin, chloramphenicol, and vancomycin)
    • Biofilm formation:
      • Protects against host defenses
      • Allows gene exchange (further promoting antibiotic resistance) 
  • Host factors that increase susceptibility:
    • Critical illness
    • Receiving lengthy courses of antibiotics
    • Hematologic malignancies
    • Solid organ transplantation

Clinical Relevance


  • Enterococci are 1 of the top 3 species causing nosocomial infections.
  • 4th most common cause of nosocomial bloodstream infections in the United States
  • 35%–40% of enterococcal bloodstream infections involve vancomycin-resistant E. faecium (VRE)

Diseases caused by enterococci

  • Often associated with:
    • Indwelling catheters
    • Surgical instrumentation
    • Underlying structural abnormalities
  • Common infections associated with Enterococcus include:
    • Urinary tract infections (most common)
    • Endocarditis
    • Bacteremia
    • Intra-abdominal and pelvic infections (often cholecystitis)
    • Wound infections
  • Other less common infections:
    • Meningitis
    • Pleural space infection
    • Skin/soft tissue infections

Organism isolation

  • Blood cultures: susceptibility testing should be included to choose appropriate therapy
  • Stool and perirectal cultures: to evaluate for VRE colonization

Antibiotic selection

  • Monotherapy:
    • May be appropriate in noncritically ill patients without endocarditis
    • Ampicillin is the drug of choice for susceptible species.
  • Combination therapy: 
    • Most commonly used in practice
    • For endocarditis and all critically ill patients
    • Cell-wall inhibitor (ampicillin, ceftriaxone, vancomycin) + aminoglycoside 
    • Often ampicillin and gentamicin
  • VRE infections:
    • Linezolid
    • Daptomycin
    • Tigecycline
  • In addition to antibiotic therapy:
    • All indwelling line and catheters should be removed.
    • Abscesses should be drained.


  1. Riedel S., et al. (2019). In Jawetz, Melnick & Adelberg’s Medical Microbiology, pp. 215–233.
  2. Murray, B., Miller, W. (2021). Microbiology of enterococci. UpToDate. Retrieved May 01, 2021, from https://www.uptodate.com/contents/microbiology-of-enterococci
  3. Murray, B., Miller, W. (2021). Treatment of enterococcal infections. UpToDate. Retrieved May 01, 2021, from https://www.uptodate.com/contents/treatment-of-enterococcal-infections
  4. Fraser S.L. (2018). Enterococcal infections treatment & management. https://emedicine.medscape.com/article/216993-treatment

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